Peptides as Therapeutic Agents for Dengue Virus

Chew, Miaw-Fang; Poh, Keat-Seong; Poh, Chit-Laa

There are a number of limitations that hinder the use of peptides as therapeutic drugs. The main challenges are due to the poor stability and bioavailability of peptides. Unmodified peptides were shown to commonly degrade quickly in human serum, resulting in low in vivo activities [183, 184] . Nonetheless, various chemical modifications can be applied to manipulate the physicochemical properties of peptides, thereby increasing the stability and bioavailability of the peptides. These chemical modification approaches have been reviewed by Gentilucci et al. (2010) [53] . For instance, conjugation to polymers such as polyethylene glycol (PEG) increased the molecular weight of peptide, hence enhancing its peripheral stability to undergo hydrolysis in the brain [185] . A previous study also showed that the half-lives of unmodified peptides of less than 0.5 hour could be increased to approximately 1.5 hour after C-amidation and N-acetylation, while cyclization successfully increased the half-lives of the peptides to 6.5 hours [186] . On the other hand, the replacement of arginine residues with an amino acid derivate of arginine, α-amino-3-guanidino-propionic acid (Agp), could dramatically reduce the cleavage of peptide by trypsin [187] . The substitution of L-amino acids to D-amino acids of pandinin-2 increased its resistance to the degradation by bovine pancreatic trypsin and human elastase. The stability of the D-amino acid substituted pandinin-2 was increased to 4 hours as compared to L-pandinin-2 which was rapidly cleaved by these two enzymes [188] .